1. Field of the Invention.
The present invention relates to a means of measuring physiological pressures, including blood pressure, intracranial pressure, intrapleural pressure (for evaluation of respiratory function and respiration rate), and pressure within the gastro-intestinal system. This invention is particularly useful for chronic measurement of pressures.
2. Description of the Prior Art
Measurement of physiological pressures is of interest to both clinicians and researchers. Such pressure measurements obtained from laboratory animals can provide researchers with valuable information with regard to the physiological response to pharmacological agents and toxicity of chemicals, and can lead to a better understanding of human physiology. The pressures which are most often of interest in animals are blood pressure, intrapleural pressure and intracranial pressure.
Blood pressure is of particular interest. Because blood pressure fluctuates over the course of time, it is often necessary to obtain chronic and frequently sampled measurements of blood pressure within a given animal in order to assess the affects of an agent over a time course. There are several methods which are currently used for chronic measurement of blood pressure. These include the tail cuff method, chronic cannulation, the use of implantable pressure sensors in combination with a telemetry backpack, and the use of vascular access ports.
The tail cuff method is well developed with several companies manufacturing devices which use this method. Some means is used to restrain the animal while an inflatable cuff is placed around the tail or leg. A blood flow sensor is typically integral to the cuff. The cuff is inflated until blood flow has ceased and is then deflated. The first indication of pulsatile flow is noted and recorded as the systolic pressure. These devices typically require that the arteries of the animal be dilated by heating the entire body of the animal to 40 degrees Celsius or more, causing significant stress on the animal and subsequent artifact. In addition, they are usually able to measure only systolic pressure. Since these devices require that the animal be restrained, artifact is introduced due to the stress of handling and restraint. In addition, it is not possible to humanely obtain measurements from an animal at frequent intervals with this method, and the method is very labor intensive.
Chronic cannulation is the most frequently used method for measurement of blood pressure for extended periods of time. With this method, a catheter is inserted into an artery. The catheter is exteriorized at a point (typically on the back of the neck) which generally prevents it from being destroyed by the animal. The catheters from a number of animals may be connected to a single pressure transducer through servo valves. A mechanical pump is typically used with each animal via a tether to continuously backflush the catheter with a heparinized saline solution. In addition, a swivel must be used on each catheter to prevent it from becoming tangled as the animal moves about the cage. The servo valves and pressure transducers are often connected to a computer to allow for frequent sampling of pressure. This method has several disadvantages. First, since the catheter is long and relatively small in diameter, the higher frequency components of the pressure waveform are often lost. Second, since the catheter is exteriorized, infections are common. Third, even though precautions are taken, the animals often become tangled in the catheter or learn to grab the catheter with their teeth or paws, and subsequently bleed to death. Fourth, keeping the catheters patent requires considerable maintenance and is thus labor intensive.
Implantable pressure sensors are sometimes used in combination with a telemetry transmitter placed in a backpack. This eliminates some of the disadvantages pointed out above. One manufacturer which supplies this type of equipment is Konigsburg Instruments (Pasadena, CA), which manufactures a number of sensors, the smallest of which is 3.5 mm in diameter. However, this sensor is too large for many applications, and since it is most frequently necessary to mount it in the wall of a vessel, it is subject to fibrous tissue growth over the sensing diaphragm which results in drift of the measured signal. In addition, the nature of the transducer is such that drift is inherent and requires frequent in-vivo calibration.
Miniature solid state sensors mounted on the tip of a catheter, such as those available from Millar Instruments (Houston, Tex.) and PPG Industries (Pleasantville, N.Y.), have also been used to measure internal body pressures. Some commercially available devices are as small as 1 mm diameter. Because of the inherent instability of these devices, they require calibration within a short time prior to use and are suitable only for acute measurements.
Another method involves implantation of a vascular access port in the animal. In this approach, a catheter is attached to a reservoir opposite a diaphragm. The catheter is placed in an artery, while the reservoir is placed under the skin to allow convenient access with a hypodermic needle. The reservoir can be accessed by piercing the skin and diaphragm with a needle. Connecting the needle to a pressure transducer allows for acquisition of pressure measurements and flushing of the catheter. The disadvantage of this approach is that it is labor intensive. A sterile protocol is required each time the diaphragm is pierced. In addition, the catheter requires bi-weekly flushing in order to maintain patentcy. If the sterile protocol is broken, the animal may develop infection, requiring expensive antibiotics and removal from the study until the infection clears. This is an expensive proposition considering that the company may have invested several thousand dollars in the animal at that point.
Intrapleural pressure is also of interest and can be used to determine the rate of respiration in addition to providing general information with regard to respiratory function. There are two methods which are commonly used to measure the rate of respiration in freely moving laboratory animals. Both methods have serious drawbacks.
One method is to use a small container which is tightly sealed, except for a controlled source of fresh air, and an exhaust port for discharge of stale air. As the animal breathes, small pressure flucuations occur within the container which can be detected by a pressure sensor. Variations in pressure can then be detected and provide a signal from which respiratory rate can be detected. This method is very accurate, but requires that the animal be placed in a cage which is often smaller than that allowed by government regulatory agencies. Therefore, it would be a violation of animal care rules to monitor respiration for more than a short time using this method.
Another method of determining respiratory rate in freely moving animals is to acquire blood pressure or electrocardiogram signals from freely moving animals and employ circuitry which can detect the modulation of these signals by respiration. The disadvantage of this method is that the modulation is often very weak or noisy. This method works relatively well on anesthetized animals, but changes in these signals caused by movement of awake animals often result in false indications.
Intracranial pressure is also of interest. Measurements of intracranial pressure from laboratory animals are often used to project which methods of treatment and management are most effective in human beings. Methods commonly used for monitoring intracranial pressure in animals include direct measurement via an exteriorized catheter or needle, or connection of a transducer to a port located on the skull of the animal. Devices such as those described by Ko (U.S. Pat. No. 4,519,401) have been used in only limited circumstances.
Chronic measurement of physiological pressures also provides vital information for clinical care of human beings. Patients with high blood pressure could benefit from an implantable device which could chronically monitor pressure as a means of determining optimal dosage for drug or bio-feedback therapy. Such a device could also be used as a means of providing feedback to a closed-loop drug delivery system for controlling blood pressure, or to a cardiac pacemaker as a means of optimizing pacing control parameters.
Infants who have been identified as being at risk for sudden infant death syndrome could also benefit. Currently, such infants are often monitored using a vest which detects changes in volume of the chest as breathing occurs. In certain instances, this method is not reliable. It would be desirable to monitor changes in intrapleural pressure as a reliable measurement of respiratory rate in these infants by a means which would allow the infant to roll and move freely about its crib without being restrained by wires extending from a vest.
Chronic monitoring of intracranial pressure is also important for infants with hydrocephalus and patients with head injury. Hydrocephalus and head injuries can cause excessive pressure build-up within the brain, resulting in death or serious brain damage. In most cases, corrective action can be taken if the build-up of pressure can be quickly detected. To detect such a build-up of pressure, a catheter is usually inserted into the brain through the skull and connected to a pressure sensor external to the patient. This offers the opportunity for infectious agents to enter along the catheter, often resulting in infections. In addition, catheters can become tangled when monitoring intracranial pressures in infants as they move about in their hospital crib. The present invention provides a means whereby chronic measurements of intracranial pressures could be obtained without the use of an exteriorized catheter.